Obesity, sedentariness and aging are known to be associated with hyperlipidemia and glucose intolerance. In order to examine the interrelationship of age, adiposity, and physical fitness to endocrine-metabolic function, a study was designed to examine glucose and lipid metabolism and sympathoadrenal function in obese sedentary men aged 45-85 years at entry into the study and again after either weight reduction or aerobic training. The three areas of endocrine-metabolic function being studied include 1) glucose tolerance and insulin sensitivity studied by the euglycemic clamp technique 2) lipoprotein metabolism as assessed by adipose tissue lipoprotein lipase activity, and 3) sympathoadrenal response to isometric exercise (handgrip), upright posture, oral glucose challenge, and hyperinsulinemia during a euglycemic clamp. To date, 27 participants have completed the baseline studies and have been randomized to either weight reduction or aerobic exercise intervention. In 10 men after a 6 plus/minus 1% weight loss, high density lipoprotein cholesterol levels increased by 19 plus/minus 4% and the LDL-C to HDL-C ratio decreased by 16 plus/minus 5% (p less than .02). In addition, in 10 middle-age to old obese sedentary men, adipose tissue lipoprotein lipase (LPL) activity decreased and triglyceride levels remained constant during a 6 hr intravenous infusion of insulin (100 mU/m2.min). In contrast, in 6 young non-obese men adipose tissue LPL activity significantly increased and plasma triglyceride levels decreased to 60% of basal. In addition, the older, obese men had significantly lower HDL and HDL2 levels than the younger participants. Whether resistance of adipose tissue LPL to stimulation by insulin is the cause of the low HDL cholesterol seen in these older obese men, will be further studied.